The randomized clinical trial is arguably one of the great advances of modern medicine. Randomized trials enable us to identify which strategies work, and which don’t, mainly because they include the critical components of proper experimental design: randomization, large sample sizes, proper follow-up, and unbiased measurements of meaningful outcomes. Unfortunately, the ability of clinical trials to generate much needed evidence now stands threatened, threatened by skyrocketing costs, excessive complexity, fragmented information, and disengaged stakeholders. Our ability to “rescue” clinical trials may well rest upon transformative business models that bring together first principles of experimentation with cutting-edge information technologies.